Interomone Compositions and Their Use to Modify Behavior in Different Vertebrate Species

ABSTRACT

A composition comprising an interomone is described for the modification of undesirable or harmful stress-related behaviors or other behaviors or physiology in a variety of vertebrate species, as well as methods of using the compositions in vertebrates from a species different than the species in which the interomone is a naturally occurring pheromone.

RELATED APPLICATION

This application relates to and claims the priority of U.S. ProvisionalPatent Application No. 61/536,673, which was filed Sep. 20, 2011 and ishereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present disclosure is broadly concerned with the field of animalbehavior and the use of pheromones and interomones. More particularly,the present disclosure is concerned with the use of a rabbit pheromone(2-methylbut-2-enal) as an interomone to produce a different behavioralor physiological effect (such as a calming or behavioral-alteringeffect) in a different vertebrate species from which the pheromone isproduced, for example, such as in dogs, cats, snakes, birds, or horses.

BACKGROUND OF THE INVENTION

Pheromones are chemicals released by living organisms that sendinformation to other organisms of the same species via scent. Pheromonesare released in response to stress, alarm, danger, sexual fertility, andin other behavioral contexts. Pheromones, by definition and according toevolutionary theory, are species-specific, that is, they are effectivein eliciting an innate response only in members of the same species.

One of the best characterized mammalian pheromones is the rabbit nipple“search pheromone.” Sensed by rabbit pups via their main olfactorysystem, the pheromone elicits a characteristic nipple search behaviorthat quickly results in the location of a nipple. (See Distel, H. andHudson, R. (1985), “The contribution of the olfactory and tactilemodalities to the performance of nipple-search behavior in newbornrabbits.” J. Comp. Physiol. [A] 157, 599-605) This guidance cue isparticularly important for rabbits, as a doe only nurses her pups foraround four minutes once a day and the quick location of a nipple in theface of sibling competition is vital for survival. This “searchpheromone” has recently been shown to be a single molecule,2-methylbut-2-enal (Schaal et al., Chemical and behaviouralcharacterization of the rabbit memory pheromone, Nature, 424:68-72,2003), which is produced in rabbit milk and is sufficient to elicit fullnipple search and grasping behavior when presented on its own atconcentrations as low as 10 ng/mL.

Chemicals that provide interspecies communication are calledallelochemicals. Some compounds are known to be a pheromone in onespecies, but have been observed to have strong behavioral effects inother species. For example, chemicals produced and released by onespecies that affect the behavior or physiology of another species to thebenefit of the originator but not the receiver are known in the art asallomones (See Grasswitz, T. R. and G. R. Jones (2002). “ChemicalEcology”. Encyclopedia of Life Sciences. John Wiley & Sons, Ltd.doi:10.1038/npg.els.0001716). The production of allomones in naturalenvironments has been mainly observed in plant species, which utilizeallomones for example to protect plants against insect herbivores.

A kairomone is another known allelochemical. It is emitted by onespecies and benefits another species, but does not benefit and oftenharms the emitter. The production of kairomones in natural environmentshas been mainly observed in insect species. For example, the PonderosaPine tree produces a terpene called myrcene when the Western pine beetledamages the tree. The emission of this chemical then lures more beetlesto the tree (See Wyatt, T. D. (2003). Pheromones and Animal Behaviour:Communication by Smell and Taste, First Edition (Cambridge, UK:Cambridge University Press).

A synomone is an allelochemical produced and released by one speciesthat benefits both the emitter and receiver. For example, plants emitodors that work to attract bees. The bees are attracted to the plants tofeed and then the bees take the pollen to fertilize otherplants/flowers.

Accordingly, the allelochemicals known in the art involve theobservation of chemicals produced by one species having an effect onanother species to the benefit and/or detriment of the emitting orreceiving species. What is described is an allelochemical that affectsthe behavior and/or physiology of another species (i.e., the receivingspecies) without additionally having a beneficial or harmful effect onthe emitting species and having a novel or unrelated behavioral orphysiological effect on the receiving species.

For instance, while domestic dogs are known to bark as part of theirnormal method of communication, dogs may show excessivebarking/jumping/mobbing/begging in response to external cues or due toboredom. Mobbing includes repetitive barking and jumping. Certain dogswill bark and jump in an excitable manner when they hear or see people,animals, vehicles, or machines. One theory is that excessive barking ispart of the “mobbing” behavior that pack animals have when they attack aprey species (Lord et al., Barking and mobbing., Behav. Processes,81:358-368, 2009).

Methods used in the art to stop the barking/jumping/begging syndromehave included shock collars, odor sprays, and loud noises, all of whichwork by startling or distracting the dog from engaging in theundesirable behavior. Dog appeasing pheromones, including syntheticcompositions believed to replicate certain calming pheromones emitted bydogs, have also been used in the art to treat certain behavioralproblems in dogs, but to date, have not been successful in alleviatingthe barking/jumping syndrome exhibited by certain dogs. Moreover, thepheromones used in the art have not been directed for use with animalspecies other than the species from which the pheromones are emitted.

Accordingly, it would be desirable to provide methods and compositionscomprising a compound known to be a pheromone in one species topositively modify animal behavioral problems in a variety of differentvertebrate species. In particular, there is a need in the art for use ofan interomone to calm, sedate, reduce anxiety, or otherwise positivelymodify the behavior of a variety of vertebrate species, including thebarking/jumping/begging syndrome exhibited by some dogs or to calmanxious dogs or cats or other vertebrate species.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel methods andcompositions for the modification of behavior in vertebrate speciescomprising compounds that have been isolated from one vertebrate speciesbut, surprisingly, have the effect of modifying the behavior in adifferent vertebrate species. Specifically, certain pheromones have beenidentified which can be made into compounds and used as part of a methodto have cross-species effects as interomones. An interomone is anynaturally secreted or synthetically produced chemical emitted as apheromone within one species, which, when isolated and administered to amember of a different vertebrate species, elicits a change in behavioror physiology of the different species without the requirement ofbenefiting and/or harming the species from which the chemical isreleased.

The present disclosure is specifically concerned with the interomone2-methylbut-2-enal (as discussed, a pheromone in a rabbit's mammarysystem) and its use in various compositions to effect a modification ofbehavior in a variety of vertebrates, for example dogs, horses, cats,snakes, and birds. 2-methylbut-2-enal is a pheromone secreted by amother rabbit to help her pups to nurse. It was surprising to learnthrough the present invention that 2-methylbut-2-enal has powerfuleffects on other species, such as dogs, and was observed to change dogbehavior.

The compositions of the invention may optionally include otheringredients as necessary or desired, depending on the form and intendeduse of the final product. Such optional ingredients can include, but arenot limited to, carriers such as water, alcohols, solvents, and thelike; fragrances, coloring agents, preservatives, antioxidants, and thelike. Examples of the resultant product include, but are not limited to,a spray, a diffuser, a spraying collar, or a collar. Alternatively, theresultant product may be an aerosol, a foam, a dip, a wipe, a cream, agel, a lotion, or a fabric garment.

Another object of the present invention is to provide a method formodifying or positively affecting the behavior of a vertebrate, themethod comprising administering a composition comprising an interomone,such as 2-methylbut-2-enal, in an amount effective to affect thebehavior of a particular vertebrate, wherein the vertebrate whosebehavior is being modified is different than that from which theinteromone is emitted as a pheromone.

Another object of the present invention is to provide for use of aformulation comprising an interomone to positively affect the behavior(e.g. calm) in a different vertebrate species. It is both unexpected andsurprising that a chemical known to be a pheromone in one species canhave a strong positive behavioral or physiological effect on members ofother vertebrate species since pheromones are, by definition, functionalonly within a particular species.

Various objects and advantages of this use will become apparent from thefollowing description taken in conjunction with the accompanyingdrawings wherein are set forth, by way of illustration and example,certain embodiments of this invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphic representation of a comparative test of dogsreceiving treatment with current calming products available on themarket (Product 1 and Product 2), a placebo, and a compositioncomprising 2-methylbut-2-enal (New Discovery).

FIG. 2 is a graphic representation of a comparative test of dogsreceiving a placebo and a composition comprising 2-methylbut-2-enal (NewDiscovery).

FIG. 3 graphically depicts statistically-significant (P<0.05)interactions observed in study 1 of Example 6. These interactionsinclude the dog pace/walk behavior (FIG. 3A), the lying down behavior(FIG. 3B), and the sitting behavior (FIG. 3C). FIG. 3D is a graphicrepresentation of overall sitting behavior in dogs over a 2 hour-periodin Study 1.

FIG. 4 is a graphic representation of the average heart rate of dogs 1-4over the periods from 2 hours before collars or sprays to 2 hours aftercollars or sprays.

FIG. 5 is a graphic representation of effects of collar or spray ofpheromone/interomone on heart rate of dogs 1-4.

FIG. 6 is a graphic representation of differential dog response to thepheromone treatments (Placebo, DAP, Serg, and RP).

FIG. 7 is a graphic representation of the relationship between dog heartrates and general activity.

FIG. 8 is a graphic representation of lying down behavior for eight dogseach given one of four treatments and startled.

FIG. 9 is a graphic representation of sitting behavior for eight dogseach given one of four treatments and startled.

FIG. 10 is a graphic representation of effects of four treatments on dogheart rates over 30 min (1,800 s) after startle. FIG. 10A shows alltreatment groups and FIGS. 10B-D compare each treatment group with thePlacebo.

FIG. 11 is a graphic representation of effects of DAPS and RP in sprayform on dog pacing-walking behaviors.

FIG. 12 is a graphic representation of effects of DAPS and RP in sprayform on dog standing behavior.

FIG. 13 is a graphic representation of effects of DAPS and RP in sprayform on lying down behavior after startle.

FIG. 14 is a graphic representation of change in surface temperature(FIG. 14A) and heart rate (FIG. 14B) of dogs 1-4 during each 30 minutescompared to the 30 minute period before startle. (Time 0=0-30 min;30=30-60 min, 60=60-90 min and 90=90-120 min after startle).

FIG. 15 is a graphic representation of effects of odors delivered byroom diffuser on standing behavior of dogs 5-8.

FIG. 16 is a graphic representation of effects of odors delivered byroom diffuser on drinking behavior of dogs 5-8.

FIG. 17 is a graphic representation of heart rate (FIG. 17A) and surfacetemperature (FIG. 17B) of dogs 5-8 when room diffusers were used for 24hours.

FIG. 18 is a graphic representation of results from a Meta-Analysis ofthree studies (Studies 1, 2, and 4) that included all 4 treatmentgroups.

FIG. 19 is a graphic representation of the effects of placebo, SERG,DAP, or Rabbit pheromone collars on dog heart rate after 24 hours.

FIG. 20 is a graphic representation of the effects of placebo, SERG,DAP, or Rabbit pheromone collars on dog heart rate after startle.

FIG. 21 is a graphic representation of the effects of placebo, SERG,DAP, or Rabbit pheromone collars on dog heart rate two hours afterstartle.

FIG. 22 is a graphic representation of the effects of pheromone collarson dog heart rate collected over 24 hours. The pheromone collars includeplacebo, Serg, RP, and a combination of Serg and RP.

FIG. 23 is a graphic representation of the effect of each treatmentcollar on individual dogs. The pheromone collars include placebo, Serg,RP, and a combination of Serg and RP.

FIG. 24 is a graphic representation of the effects of pheromone collarson dog heart rate while startled. FIG. 24A shows the main effects ofSerg and RP collars. FIG. 24B shows the effects of Serg, RP, and Serg/RPcombination collars.

FIG. 25 is a graphic representation of the dog response to the RPcollar.

DETAILED DESCRIPTION OF THE INVENTION

The broad term, interomone, is used herein to refer to chemicals emittedas pheromones within one vertebrate species that influence the behavioror physiology of a different species without the requirement ofbenefiting and/or harming the emitter or receiving species (although aninteromone could benefit or harm the emitting or receiving species). Thesurprising use of specific pheromones having a cross-species effectwithout providing any benefit or harm to the emitting species has notheretofore been developed.

The present invention relates to the use of 2-methylbut-2-enal in acomposition as an interomone, rather than as a rabbit pheromone as it isknown and used in the art, in order to affect the behavior of differentvertebrate species (such as, for example, dogs, cats, horses, frogs,snakes, birds, etc.). One of skill in the art will appreciate thatadditional pheromones not specifically disclosed herein may be found tohave differential and perhaps beneficial effects in other species, suchas, pheromones from other mammals (e.g., cats, tigers, lions, elephants,hamsters, mice, and rats), pheromones from reptiles (e.g., snakes andlizards), pheromones from birds, or pheromones from amphibians.2-methylbut-2-enal has been formulated into a composition as aninteromone for administration to different species (such as, forexample, the horse, dog, cat, and other vertebrates) in order topositively modify the behavior of members of the different species.

In particular, administration of 2-methylbut-2-enal as an interomone todogs surprisingly results in reducing activity or positively modifyingthe behavior of dogs that exhibit the anxious behaviors.

The present disclosure provides for a composition comprising aninteromone, which is a chemical or compound related thereto emitted byone species and known to be a pheromone within that species to modifythe behavior of different vertebrate species. When the compositioncomprising the interomone is applied to or in the vicinity of differentvertebrate species, the animal is calmed for a period of time. It isunexpected and surprising that a natural compound found in onevertebrate species can have a large, meaningful effect on members ofanother vertebrate species since pheromones are, by definition,species-specific. Androstenone (as disclosed in U.S. application Ser.No. 13/623,279, filed on Sep. 20, 2012) and 2-methylbut-2-enal are twoexamples that work in a cross-species manner. Other chemicals and theircross-species beneficial use may become apparent to those skilled in theart following the teachings of the present invention.

I. Formulations

The formulations of the present invention may comprise a chemical thatis naturally secreted, isolated from a secretion, or syntheticallyduplicated from a vertebrate species. The chemicals that may be used inaccordance with the present invention are those that produce a certaineffect within the species from which they are secreted and a differenteffect when used in another species.

The formulations of the present invention comprise an interomone. In apreferred embodiment, 2-methylbut-2-enal is used as an interomone. The2-methylbut-2-enal used in the compositions may be the natural pheromonesecreted or isolated directly from a rabbit, or a synthesized compoundcharacterized by the following structural formula (Includingenantiomers, diastereomers, or racemates thereof):

The amount of 2-methylbut-2-enal in the formulation will be an amounteffective to positively modify or alter the behavior (e.g., calm, reducenervousness, or lower the heart rate) of a particular animal. Generally,the amount of 2-methylbut-2-enal in the formulation should be at least0.001% (w/w) of the total composition. In one embodiment, theconcentration of 2-methylbut-2-enal in the composition ranges frombetween about 0.001% to about 1% (w/w). In another embodiment, theconcentration of 2-methylbut-2-enal in the composition ranges frombetween about 0.01% to about 0.1% (w/w). Preferably, the concentrationof 2-methylbut-2-enal present in the composition ranges from betweenabout 0.01% to about 0.05% (w/w) and most preferably the concentrationof 2-methylbut-2-enal in the composition is about 0.01% (w/w).

In one embodiment, the composition of the present invention contains2-methylbut-2-enal. In another embodiment, the composition contains acombination of 2-methylbut-2-enal and at least one additional pheromonecomposition. For instance, the composition may comprise2-methylbut-2-enal and at least one additional pheromone composition,such as the composition described in U.S. Publication No. 2011/0150822.

In addition to an interomone, the formulations may optionally containadditional components such as solvents, propellants, surface-activeagents, thickeners, and fragrances (i.e., “additional components”). Theformulation may include one additional component or a combination of anyof the forgoing additional components in varying amounts. Suitableexamples of each type of additional component are detailed below.

In a preferred embodiment, the formulation includes at least one carriersolvent. Suitable carrier solvents are generally known within the artand are recognized to include lipophilic organic diluents, alcohols,ethylene glycol, propylene glycol, dipropylene glycol, ether,chloroform, benzene, carbon disulfide, oils including non-volatile andvolatile liquids and oils, water, and combinations thereof. For example,an interomone can be dissolved in a suitable alcohol and supplied in aliquid form such as a pump spray or for use in a plug-in diffuser.Suitable alcohols include ethanol, propanol, isopropanol, butanol,pentanol, hexanol, heptanol, octanol, and phenyl ethyl alcohol. In apreferred embodiment, the alcohols comprise ethanol, isopropanol,butanol, and phenyl ethyl alcohol. An alcohol solvent can be combinedwith water or a lipophilic organic diluent or carrier such as ethyleneglycol, propylene glycol, dipropylene glycol, dipropylene glycolmonoethyl ether, dipropylene glycol methyl ether, or Dow Corning®Q7-9180 silicone liquid. In a preferred embodiment, the solvent is acombination of water and an alcohol selected from the group consistingof ethanol or isopropanol. In a one embodiment, the amount of solventpresent in the composition ranges from between about 0.5% and 99.99%(w/w) of the composition. Preferably, the amount of water present in thecomposition ranges from between about 70% and about 99.99% (w/w) of thecomposition and most preferably ranges from between about 80% and about98.5% (w/w). Preferably the amount of alcohol present in the compositionranges from between about 1% and about 20% (w/w) and most preferablyranges from between about 1.5% and about 10% (w/w).

The formulation may additionally include a propellant. Suitablepropellants include chlorofluorocarbons (CFC) such astrichloromonofluoromethane, dichlorodifluoromethane, anddichlorotetrafluoroethane; hydrochlorofluorocarbons (HCFC) orhydrofluorocarbons (HFC) such as chlorodifluoromethane,trifluoromonofluoroethane, chlorodifluoroethane, difluoroethane, andheptafluoropropane; hydrocarbons such as propane, butane, and isobutene;and compressed gases such as nitrogen, carbon dioxide, and nitrousoxide, as well as combinations of any of the above describedpropellants. In one embodiment, the propellant is propane. In anotherembodiment, the propellant is 1,1-difluoroethane. The propellant doesnot comprise an inert gas of Tumorigen compound class, which includes1,1,1,2-tetrafluoroethane, chlorodifluoromethane, anddichlorodifluoromethane. Preferably, the propellant has a flash point ofless than about −50° C. Generally, when a propellant is included in thecomposition, such will range from between about 75% to about 99.99%(w/w) of the composition, preferably between about 85% and about 99.99%(w/w), and most preferably from between about 95% and about 99.99%(w/w).

The formulation may optionally include one or more surface-active agents(also called surfactants). Surfactants are generally used in preparingthose embodiments of the present invention directed to compositions thatare formulated as emulsions. Either water in oil or oil in wateremulsions may be formulated. Examples of suitable surfactants include:nonionic ethoxylated and nonethoxylated surfactants, abietic acid,almond oil PEG, beeswax, butylglucoside caprate, C18-C36 acid glycolester, C9-C15 alkyl phosphate, caprylic/capric triglyceride PEG-4esters, ceteareth-7, cetyl alcohol, cetyl phosphate, corn oil PEGesters, DEA-cetyl phosphate, dextrin laurate, dilaureth-7 citrate,dimyristyl phosphate, glycereth-17 cocoate, glyceryl erucate, glyceryllaurate, hydrogenated castor oil PEG esters, isosteareth-11 carboxylicacid, lecithin, lysolecithin, nonoxynol-9, octyldodeceth-20, palmglyceride, PEG diisostearate, PEG stearamine, poloxamines,polyglyceryls, potassium linoleate, PPG's, raffinose myristate, sodiumcaproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate,sodium tocopheryl phosphate, steareths, TEA-C12-C13 pareth-3 sulfate,tri-C12-C15 pareth-6 phosphate, and trideceths.

In certain applications, it may be desirable to thicken the formulation.Suitable examples of thickening or viscosity increasing agents, includeagents such as: acrylamides copolymer, agarose, amylopectin, bentonite,calcium alginate, calcium carboxymethyl cellulose, carbomer,carboxymethyl chitin, cellulose gum, dextrin, gelatin, hydrogenatedtallow, hydroxytheylcellulose, hydroxypropylcellulose, hydroxpropylstarch, isopropyl palmitate, magnesium alginate, methylcellulose,microcrystalline cellulose, pectin, various PEG's, polyacrylic acid,polymethacrylic acid, polyvinyl alcohol, various PPG's, sodium acrylatescopolymer, sodium carrageenan, xanthan gum, and yeast beta-glucan. Theamount of thickener present in the formulation may range from betweenabout 1% to about 30% (w/w), preferably from between about 5% to about20% (w/w), and most preferably from between about 10% to about 15%(w/w).

The composition may additionally comprise a fragrance. The fragrance maybe any fragrance that provides a desired odor masking effect since aparticular interomone may have a pungent odor. Although a variety offragrances may be employed without departing from the scope of thepresent invention, suitable fragrances include floral essences, citrusblossoms, oil or extracts of conifers, or spices. Examples of floralessences include rose, lilac, lavender, gardenia, and jasmine. Suitablecitrus blossoms include orange and lemon, and suitable oil or extractsof conifers include pine and juniper. Generally, fragrance may comprisebetween about 0.25% and about 1% (w/w) of the composition.

II. Routes of Administration

Mammals, including dogs, have several anatomical organs that receiveolfactory signals. The two most dominant “smell” organs are the mainolfactory epithelium (MOE) and the vomeronasal organ (VNO). Othersensory fibers are in the nasal cavity that can sense odors, but themain olfactory bulb and accessory olfactory bulb (receiving signals fromthe VNO) are the major integrating systems.

The olfactory bulb lies at the front of the brain. It sends neuronalprojections through a bone and extends these projections into theolfactory epithelium. The MOE is an extensive area with a rich bloodsupply and mucosa in which odor aerosol molecules pass on their way tothe lungs. Odor or water droplets will settle on the MOE, and if an odorreceptor is present, that odor receptor will be bound and causeactivation of the sensory neurons. Among all the genes in the mammalianbody, the olfactory receptors have the largest number of genes. Thisindicates the importance of olfactory communication in animals, some ofwhich seems to be lost in humans.

Administration of the interomone composition to a subject animal istypically accomplished through any method allowing for delivery of aneffective amount of the interomone via inhalation by the animal. Suchmethods of administration include, for example, placing or distributingthe composition comprising the interomone in the environment of theanimal, either by incorporating the composition into a wearable devicesuch as a collar, or by applying (e.g. spraying or wiping) thecomposition to surfaces in the living environment of the animal ordirectly onto the animal, such as to its facial region or head. Forexample, the interomone composition may be administered topically to ananimal using an aerosol, pump spray, foam, collar, wipe, dip, liquid,gel, lotion, and/or cream. The term “effective amount” describes anamount of interomone present in a composition that is sufficient toproduce a noticeable modification, i.e. improvement, of animal behaviorin the subject animal, as determined according to behavioralobservations as described herein. The effective amount will depend onfactors such as the severity of the behavior being treated; individualanimal parameters including age, physical condition, size and weight;concurrent treatments; the frequency of treatment; or the mode ofadministration. These factors are well known to those of ordinary skillin the art and can be addressed with no more than routineexperimentation.

In one embodiment, the interomone can be incorporated in various ways asare generally well known into a solid carrier material to form a collaror tag, and the collar or tag is then worn by the animal. The solidcarrier material is selected from among those materials, typicallypolymeric compounds, generally recognized to be suitable for release ofactive compounds and set forth in further detail herein below.Alternatively, the interomone can be combined with a solvent to form aliquid solution and the liquid solution can be further prepared invarious formulations suitable for delivery to the animal by inhalation.For example, liquid solutions can be further prepared according tomethods well known in the art such as a pump spray, aerosol, gel, foam,shampoo, dip, cream, lotion, gel, diffuser, or spot-on formulation.

In a preferred embodiment, 2-methylbut-2-enal is dissolved or diluted ina nonaqueous organic solvent or solvent mixture to form a solution forincorporation into a pump spray containing the interomone. The solutionmay optionally be combined with at least one additionalpheromone/interomone or pheromone/interomone composition. A preferredpump spray solution will comprise about 0.01% (w/w) 2-methylbut-2-eanl,about 10% (w/w) isopropyl alcohol and about 89% (w/w) water.Additionally, between about 0.5% and 1% (w/w) of a fragrance may beadded to the solution.

In a further embodiment, 2-methylbut-2-enal is dissolved or diluted witha solvent and a thickener to form a solution for use in a diffuser. Thesolution may optionally be combined with at least one additionalpheromone/interomone or pheromone/interomone composition. A preferreddiffuser solution will comprise about 0.02% (w/w) 2-methylbut-2-enal,between about 80% to about 85% (w/w) solvent, about 15% (w/w) thickener.Additionally, between about 0.25% and 1% (w/w) of a fragrance may beadded to the solution.

In an additional embodiment, 2-methylbut-2-enal may be incorporated intoa solid carrier material to form a matrix composition containing theinteromone (or interomone combined with at least one additionalpheromone/interomone or pheromone/interomone composition), such as afabric garment or a collar. The matrix containing the interomone may beformed into a collar as is well known and amply described in the art,for example in U.S. Pat. No. 3,852,416. Typically an admixture of anactive (i.e., an interomone) and a carrier material providing the matrixis formed into strips through an extrusion process, and each strip isthen formed a collar by including a fastening device such as a buckle,snap or hook. The solid carrier material forming the matrix into whichthe interomone is incorporated is for example a polymer or polymermixture with suitable release characteristics such that the pheromone isreleased from the collar to be inhaled by the animal. Additionally, thematrix containing the interomone may be formed into a fabric garment asis described in the art, for example in U.S. Publication No.2010/00319632. The interomone preferably contributes from between about0.001% and about 1% (w/w), and preferably between about 0.01% and 0.5%(w/w) of the collar or fabric garment.

Suitable polymers for forming a solid substrate for making a collar arewell known and include, but are not limited to, polyethylene, polyvinylacetate, ethylene acid copolymers, ethylene acrylates, polyurethanes,styrene-butadiene, polyvinyl butyral, polyvinyl chloride (PVC),polyolefin, polyacrylate, and polymethacrylate esters, and siliconpolymer. The polymers can contribute between about 50% to about 99.99%(w/w) of the collar, and typically will contribute between about 90% andabout 99.99% (w/w) of the collar. Plasticizers can be incorporated intothe mixture to render the polymer resin more flexible. Suitableplasticizers include phosphoric acid esters (e.g. tricresyl phosphate)or phthalic acid esters (such as dioctyl phthalate or diisodecylphthalate (DIDP)). The collar may also include other additives such asstabilizers, for example antioxidants to protect the collar materialfrom degradation by UV light and other oxidizing factors. Lubricants,colorants, and fillers may also be included.

Iii. Methods of Using an Interomone to Modify Behavior in an Animal

The present invention is further directed to a method of usinginteromones to positively modify undesirable or inappropriate behaviors(e.g., barking, jumping, begging, and/or mobbing) or physiology in ananimal by exposing the animal to an effective amount of aninteromone-based composition, wherein the composition comprises at leastabout 0.001% (w/w) of an interomone. Generally, the compositioncomprises between about 0.001% and about 1% (w/w) of an interomone. Theanimal can be exposed to the composition by any method allowinginhalation by the animal over a period of time sufficient to effect amodification of the target behavior, as determined according tobehavioral observations. Typically, depending on the chosen route ofadministration, the particular animal, and situation, the exposure ofthe composition to the animal will be over a period of at least onesecond, but can also be for a period of at least one hour, for a periodof between one hour and five hours, for a period of at least one day,for a period of at least one week, for a period of between one week andfour weeks, for a period of at least one month, or for any period oftime as may be needed to achieve a satisfactory behavioral effect. Forexample, an animal suffering from a temporarily induced anxiety (e.g., atrip to a veterinary office, being handled, or fireworks), may require abrief exposure to the composition before, during or after theanxiety-inducing event to relieve the anxiety and associated behavior.In contrast, an animal exposed to a stressful stimulus for a longer andcontinual period, such as a pet exposed to a new pet in the household,may benefit from regular exposure to the interomone composition for anextended period.

Commonly recognized sources of stress in animals include for exampleweaning, transportation (especially in motorized vehicles), boredom,lack of exercise, separation anxiety, loud noises, events that inducebarking/jumping/begging or anxiety, introduction to new people oranimals, and visits to a veterinary office. Animals that are stressed byexposure to such events or conditions will typically exhibit highlyundesirable stress-related behavioral symptoms. Such undesirablebehaviors are commonly recognized and include for example fearfulbehavior such as cowering or shaking; excessive chewing, barking,begging, pacing, or excessive laying down; hyperactivity such asjumping; aggressive behavior toward people or other animals such asgrowling, snappishness or biting; property destruction; and frequenturination or soiling. The efficacy of the interomone composition can betested for example by spraying subject animals with an aerosol sprayincorporating the composition, having the subject animals wear a collarincorporating the composition, or by applying the composition in theform of a liquid diffuser or the like in a physical area associated withthe stress-inducing conditions for any given animal. In any case, thecomposition is sufficiently volatile for the animal to inhale and thusbe exposed to a sufficient amount of the composition to produce anoticeable behavioral effect. For example, a reduction in undesirableoutward behaviors is readily ascertainable (e.g. noticeable reduction inaggressive displays, barking and/or jumping) and can be supplemented byobserving other physical indicators of stress such heart rate, weightchanges, and secretion of stress hormones such as cortisol. Whenundesirable behaviors are observed, the composition of the presentinvention may be used to induce a temporary state of lower activity,calm and reduced excitability.

In use, the composition comprising an interomone can be implemented in anumber of different ways depending in part on the targeted animals andbehavior desired to be modified. For example, an exemplary liquid sprayformulation containing 2-methylbut-2-enal (dissolved in a suitablesolvent) can be sprayed, for example, on the animal's nostrils, face,head or in its environment such that it may be perceived througholfaction as frequently as needed to obtain the desired behavioralmodification. For example, an exemplary a liquid formulation containing2-methylbut-2-enal can be delivered by way of a diffuser, such as aplug-in diffuser commercially available from as Central LifeSciences/Farnam Companies Inc. (Phoenix, Ariz.) as the Comfort Zone®Diffuser (sold with Feliway® or DAP® (Dog Appeasing Pheromone)).Alternatively, an interomone in liquid, gas, or solid form can beincorporated in a plasticized material such as PVC or the like that canthen be formed into a tag, or in strips to form a collar. Furthermore,the interomone composition can be combined with at least one additionalpheromone/interomone or pheromone/interomone composition (natural orsynthetic) prior to implementation into any of the above-mentioned modesof delivery to the animal.

It should be understood that the interomone used in the composition maybe provided in the form of pure concentrate (100% concentration) or adiluted composition with additional excipients in the dosage form (i.e.the amount of active ingredient in the composition is less than or equalto 99.99%, and the remainder consists of inactive excipients). Ifdiluted, the amount of interomone dispensed in the various dosage formsmay range from between about 1.0 pg/mL to about 1.0 g/mL, morepreferably between about 1.0 ng/mL to about 1.0 g/mL. One of skill inthe art will appreciate that the volume of active component added to thecomposition will need to be adjusted to account for the dilution and toensure the end composition comprises the appropriate final concentrationof interomone. One of skill in the art will also appreciate that thevarious components of the composition may be provided in a variety ofdosage forms including, but not limited to liquid solution orsuspension, emulsion, aerosol, slow release matrices, and the like.

The compositions according to this invention may be applied in a varietyof ways but are best applied by exposing the olfactory system by anymeans such as, for example, spraying a light mist directly on the facialregion or in the environment of the animal whose behavior is intended tobe modified. Further, the methods of the current invention are bestaccomplished by allowing the animal to inhale the composition, as thenasal cavities, sinuses, lungs and throats of animals present a largearea for the aromatic molecules to be bound to an olfactory receptor.The application of the composition to the animal or the animal'senvironment may be repeated as often as necessary to modify the animal'sbehavior.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as is commonly understood by one of skill in theart to which this invention belongs at the time of filing. Ifspecifically defined, then the definition provided herein takesprecedent over any dictionary or extrinsic definition. Further, unlessotherwise required by context, singular terms shall include pluralities,and plural terms shall include the singular. Herein, the use of “or”means “and/or” unless stated otherwise. All patents and publicationsreferred to herein are incorporated by reference.

As used herein, “a” and “an” mean one or more, unless otherwiseindicated.

As used herein, “interomone” means any naturally secreted orsynthetically produced chemical released by one species, which, whenadministered to a member of a different vertebrate species, elicits achange in behavior or physiology of the different species with orwithout providing a benefit or harm to the species from which thechemical is released.

As used herein, “vertebrate” or “vertebrate species” is interchangeablewith the word “animal” or “animal species” and encompasses any group ofanimals distinguished by possession of a vertebral column. Examples ofvertebrate species include, but are not limited to, domestic animalssuch as cats and dogs; small animals, such as hamsters, rabbits,ferrets, rats, mice, and guinea pigs; commercial animals, such ashorses, sheep, cattle, and swine; animals in captivity, such as apes,chimpanzees, tigers, lions, bears, elephants, zebras; amphibians such asfrogs and salamanders; reptiles such as snakes, turtles, crocodiles,alligators, and lizards; birds, and the like.

Although the invention described herein is susceptible to variousmodifications and alternative iterations, specific embodiments thereofhave been described in greater detail above. It should be understood,however, that the detailed description of the use of Androstenone is notintended to limit the invention to the specific embodiments disclosed.Rather, it should be understood that the invention is intended to coverall modifications, equivalents, and alternatives falling within thespirit and scope of the invention as defined by the claim language.

EXAMPLES Example 1 Preparation of Spray Composition Comprising2-methylbut-2-enal for Use on Dogs

A pump spray formulation comprising 2-methylbut-2-enal was prepared inaccordance with the formulation set forth in Table 1.

TABLE 1 Pump Spray Composition Comprising 2-methylbut-2-enal asInteromone Ingredient % grams 2-methylbut-2-enal 0.01 0.01 IsopropylAlcohol 10.00 10.00 Lavender Chamomile fragrance 0.50 0.5 #AA101592 D.I.water 89.49 89.49 Total 100.00% 100

Example 2 Determining the Efficacy of a Spray Composition Comprising anInteromone in Modifying Behavior of Dogs

A spray composition comprising 2-methylbut-2-enal as an interomone wasprepared in accordance with Example 1.

Four dogs were fitted with cloth jackets that contained electrodes tomeasure their heart rate. One dog was sprayed with the2-methylbut-2-enal composition, one dog was sprayed with a placebo, andtwo dogs were sprayed with pheromone-based products currently on themarket for purposes of modifying behavior. The dogs in each group weresprayed in the face to ensure the dog had an olfactory experience withthe liquid formulations. Data were collected for two hours followingapplication of the spray to the facial/snout region of the four dogs.The control period was indicated as time zero (“0”) on FIG. 1 and FIG.2.

As shown in FIG. 1, the spray containing the 2-methylbut-2-enal wasfound to reduce the average dog heart rate 24.5 beats/min per hour andreduced heart rate by 30% over the two hour period when compared to theproducts currently on the market and the placebo. FIG. 2 compares theeffect of the spray containing the 2-methylbut-2-enal with the placeboto emphasize the greater reduction in heart rate when the dogs wereexposed to the interomone product of the present disclosure over thetwo-hour period.

Example 3 Preparation of a PVC Collar Containing 2-Methylbut-2-Enal asInteromone for Use on Dogs

A collar containing 2-methylbut-2-enal can be prepared according totypical industry techniques as described hereinabove. Table 2 is thelist of ingredients that can be used to prepare a collar comprising arabbit pheromone.

TABLE 2 Collar Comprising 2-methylbut-2-enal as Interomone Ingredient %grams 2-methylbut-2-enal 0.02 0.02 MU-760000 (Microthene) 99.780 99.780Corona magenta - Pink (DayGlo) 0.100 0.100 Blue #2 (DayGlo) 0.100 0.100Total 100.00% 100

Example 4 Preparation of a PVC Collar Containing 2-Methylbut-2-Enal andan Additional Pheromone for Use on Dogs

A collar containing 2-methylbut-2-enal and an additional pheromonecomposition can be prepared according to typical industry techniques asdescribed hereinabove. Table 3 is the list of ingredients that can beused to prepare a collar comprising a rabbit pheromone and an additionalpheromone composition.

TABLE 3 Collar Comprising 2-methylbut-2-enal as Interomone and anAdditional Pheromone Ingredient % grams 2-methylbut-2-enal 0.02 0.02MU-760000 (Microthene) 93.88 93.88 Pheromone H (ModernVeterinary 6.006.00 Therapeutics, Florida) Blue #2 (DayGlo) 0.100 0.100 Total 100.00%100

Example 5 Preparation of a Room Diffuser Containing 2-Methylbut-2-Enaland Use on Dogs

A room diffuser formulation containing 2-methylbut-2-enal can beprepared according to typical industry techniques described above. Table4 is the list of ingredients that can be used to prepare a diffuserformulation comprising a rabbit pheromone.

TABLE 4 Diffuser Formulation Comprising 2-methylbut-2- enal asInteromone Ingredient % grams 2-methylbut-2-enal 0.02 0.02 IsopropylPalmitate 15.00 15.00 Lavender Chamomile frag. 0.5 0.5 #AA101592 QC-9180Silicone Fluid 0.65 CS 84.48 84.48 Total 100.00% 100

Example 6 Determining the Efficacy of 2-Methylbut-2-Enal as anInteromone in Adult Dogs When Administered in Liquid (Spray and RoomDiffuser) Form

Four distinct studies were conducted for purposes of examining anddetermining the efficacy of 2-methylbut-2-enal, a rabbit maternalpheromone, as an interomone in dogs when administered in liquid form(e.g., spray and room diffuser).

Eight dogs were obtained from a local contract research facility andassessment was made as to general dog health, behavior and heart rate.The dogs were estimated to be 2 to 7 years of age, mixed breed, andweighed averagely 8.1±0.18 kg at the start of the studies. The averagebody weight and feed intake of the dogs did not significantly changeover the course of the studies. Upon arrival each dog was bathed usingshampoo containing flea and tick medicine (Hartz Mountain Corp.Secaucus, N.J. USA), and their body hair was shaved. Each dog was keptin a single room, which had 100% fresh air intake and exhaust. The dogswere fed twice (am and pm) per day ad libitum. At that time, the roomwas cleaned and the dogs obtained extra exercise. Water was available adlibitum.

Dog sex, behavior, and average heart rate are provided in Table 5. Asshown in Table 5, all eight dogs were generally nervous types and variedin other behaviors such as shy, aggressive or pacing.

TABLE 5 Dog Sex and Behavioral Types. Dog Avg Heart number Sex Rate*Behavioral Type 1 Male 204.9 Nervous 2 Male 117.0 Nervous, aggressive,biting 3 Male 140.0 Nervous, pacing 4 Male 137.9 Nervous, shy 5 Male140.6 Nervous, pacing 6 Female 78.4 Nervous, inactive 7 Male 81.8Nervous, runs away from people 8 Female 65.4 Nervous, head down, avoidspeople, difficult to catch *SE pooled = 10.7 bpm. Dogs 1-4 were presentat one period while dogs 5-8 were present about 8 weeks later. Amongdogs used in the collar/spray study, dog 1 had elevated basal HR. Amongdogs used in the room diffuser study, dog 5 had elevated HR compared tothe other three dogs (6-8).

Dog behavior was captured on video media at a sampling rate of 30 framesper second. Video records were reviewed in real time (with tape playing30 frames per second). A scan sampling method was used to record dogbehaviors each minute or each 5 minutes depending on the particularstudy. If the sample period was 120 minutes with four periods (0-30=0,30-60=30, 60-90=60, and 90-120-90 min), then a scan sample was recordedeach 1 minute. If the sample period was 24 hours, then the scan samplewas collected each 5 minutes and summarized each hour. A list ofobserved dog behaviors and their definitions are provided in Table 6.For example, pacing is when a dog walks in a stereotyped manner forminutes to hours. Because it was not easy to distinguish walking frompacing, the behaviors were merged. In addition, the video records couldnot clearly distinguish lying down and awake versus lying down andsleeping, therefore there was no separate description for these twobehaviors.

TABLE 6 Definitions of Behaviors Used in This Study Behavior DefinitionPace-walk Locomotion in any pattern Stand Supported by limbs, notmoving/walking/pacing Sit Posterior on ground while front feet supportthe animal Lying down Dog's body not supported by any limb. Lick selfTongue touching any self body part Eat Head in dog bowl Drink Head inwater bowl Urinate Urine stream observed Defecate Defecation observedActivity Obtained by calculation; all behaviors other than lying down;also, the inverse of lying down.

Heart rate during the studies was measured by the use of a non-invasivetelemetry system (Data Science International, St. Paul, Minn., USA).Leads were placed in contact with the dogs' shaved skin. Sensorsmeasured heart rate, surface temperature and general activity. Data weretransmitted to a receiving computer in another room. The sampling ratevaried with the study, but was 5 seconds for the first two hours aftertreatments and then each 1 minute for 24 hours (depending on theparticular study). For surface temperature measurements of the dogsubjects, a thermistor was located against the skin of each dog. Itrecorded the surface temperature to the neared 0.1° C. on the sameinterval as the heart rate data.

Behavior and physiological data (heart rate and surface temperature)were analyzed by least squares analysis of variance using SAS (2011)software and the general linear models procedures. The experimentaldesign of each study was a specialized randomized complete block in aLatin square design with data collected as a split plot over time. Dogsrepresented the blocks. Each dog received each treatment randomly insuccessive days or weeks. The statistical model included effects oftreatment (TRT), dog, dog by treatment (TRT*DOG; error term used toassess treatment and dog effects), time (HR), treatment by time(TRT*HR), and residual error (SE; used to test remaining effects).Behavior data were collected and analyzed as counts per time period, butfor clarity of presentation, the data are reported as percentage of timedogs engaged in each behavior.

Studies and Results Study I

In Study 1, baseline heart rate data were collected while the dogs eachexperienced 4 different treatments—a placebo collar (PLACEBO), Pheromone“H” Collar (SERG), Dog Appeasing Pheromone in collar form (DAPC) and theRabbit Pheromone (RP; 1 μg/mL) formulated into a spray in accordancewith Example 1. Each of the four treatments was given to each dog in arandom order, with the treatment changing each week. Baseline heart rateand behavior data were collected for 30 minutes before each treatmentapplication (see Table 7) and 2 hours after (see Table 8) (expressed in% of time).

TABLE 7 Difference Among Dogs in Baseline Behavior Lick Dog PW Stand SitLying self Eat Drink Defecate Urinate 1 0.0% 2.8% 55.0% 76.7% 0.0% 0.0%0.0% 0.0% 0.0% 2 0.0% 0.0% 35.8% 85.6% 0.0% 0.0% 0.0% 0.0% 0.0% 3 36.1%0.0% 58.3% 58.9% 0.0% 8.3% 0.0% 0.0% 0.0% 4 0.0% 0.0% 13.9% 94.4% 0.0%0.0% 0.0% 0.0% 0.0% 5 19.4% 13.9% 83.3% 52.2% 0.0% 0.0% 2.8% 0.0% 0.0% 60.0% 0.0% 0.0% 100M 0.0% 0.0% 0.0% 0.0% 0.0% 7 50.0% 0.0% 25.0% 60.0%0.0% 25.0 0.0% 0.0% 0.0% 8 0.0% 0.0% 0.0% 100.0% 0.0% 0.0% 0.0% 0.0%0.0% SE 11.5% 2.9% 29.7% 14.3% 0.0% 6.1% 1.0% 0.0% 0.0% P- 0.06 0.040.46 0.17 . 0.22 0.51 . . value

TABLE 8 Baseline Dog Behaviors (% of time) During 120 minutes AfterTreatment Behavior PLACEBO SERG DAPC RP SE TRT TRT*DOG TRT*HR Pace-walk13.4 12.2 24.3 7.6 10.4 0.71 0.0037 0.18 Standing 2.2 9.0 12.5 3.1 3.40.14 0.052 0.17 Sitting 33.6 47.6 68.1 93.1 22.4 0.29 0.001 0.016 Lyingdown 78.6 71.9 58.0 58.5 10.0 0.40 0.001 0.52 Lick self 0 0 0 0 0 — — —Eat 4.1 1.4 0.0 0.0 1.6 0.25 0.079 0.090 Drink 0.3 0.0 0.0 0.0 0.2 0.500.48 0.42 Defecate 0 0 0 0 0 — — — Urinate 0 0 0 0 0 — — — DAPC = DogAppeasing Pheromone in collar form; RP = Rabbit pheromone, SERG =Sergeant's pheromone collar; TRT = Pheromone/interomone treatment; HR =hour or time; SE = residual error.

Results as to Behavior:

The overall treatment effects were not statistically significant (seeTable 8), however a large number of treatment by dog (TRT*DOG) effectsand one treatment by hour (TRT*HR) effect were identified as indicatedin Table 8. Some dogs responded to some treatments differently.

The statistically-significant interactions set forth in Table 8(pace-walk, lying down, and sitting) are represented in FIGS. 3A, 3B,3C, and 3D. FIG. 3A illustrates pacing-walking behavior following thedifferent treatments. Some dogs did not pace. Dogs 4, 6, and 8 showedlittle or no pacing. Dog 1 showed increased pacing-walking when itexperienced the DAP collar (DAPC); Dog 3 showed increased pacing-walkingwhen it experienced the SERG collar in comparison to DAP collar or RPspray; and that, relative to the Placebo collar, dog 7 showed reducedpacing-walking compared with the DAP collar or RP spray.

Lying down behavior was also compared to the dogs' general activity.Dogs 3, 4, 5, 6, and 7 were not significantly influenced by treatments.However, the significant dog treatment interaction (P<0.001) wasexplained by differential effects on treatments among dogs 1, 2, and 8as illustrated in FIG. 3B. Compared with the Placebo treatment, dog 1had reduced lying down with the DAP collar, meaning that the DAP collarincreased this dog's activity. For dog 2, both SERG and RP reduced lyingdown behavior significantly and increased the dog's activity. For dog 8,only RP increased dog activity and reduced lying down compared with theplacebo treatment.

Sitting behavior is represented in FIG. 3C for the four dogs in whichsitting differed between treatments and the placebo (dogs 2, 3, 7 and8). SERG collar increased sitting only in dog 2. RP spray increased dogsitting in dogs 2 and 8 compared to the Placebo. The DAP collarincreased sitting behavior in dogs 3, 7 and 8. Dog sitting behavior wasfurther influenced by the effects of treatment over time (i.e., the2-hour period after collar or spray application) as shown in FIG. 3D.When dogs experienced the Placebo, they sat down less over time (fromnearly 30% of their time to 10% or less). In contrast, in the 30 minuteperiod after rabbit pheromone spray, dogs sat an average of nearly 50%of the time. In the 60 minute period after treatment with rabbitpheromone, dogs also sat more than with the other treatments, includingthe Placebo. At the 90 minute period after DAP collar application, dogssat more than dogs given the placebo collar. These results demonstratedthat the rabbit pheromone spray calms dogs faster than treatment withDAP collar.

Results as to Heart Rate:

Using data collected through the entire study period, all threetreatments were found to generally decrease overall dog heart rate (HR)in dogs 1-4 as shown in FIGS. 4, 5, and 6. However, the rabbit pheromonetreatment most significantly (P<0.05) reduced overall dog heart rate(see FIGS. 4 and 5). Dog heart rates did not differ when first exposedto any odor; however, the dogs experiencing rabbit pheromone by sprayhad a greater decline in heart rate than Placebo (see FIG. 5). Alltreatments resulted in a significant (P<0.05) decrease in heart rateover the two hour period after collar application. However, the dogsexperiencing rabbit pheromone by spray had a greater decline in heartrate than the Placebo in the first two hours after pheromone application(see FIG. 5).

The regression equations for each line are given in the legend to FIG.5. The slopes of the equations represent the speed of the heart ratedecline under each treatment. Placebo-treated dogs had a heart ratedecline of 6 bpm/h, while the decline in heart rate for the SERG collarwas 8.5 bpm/h. The DAP collar-treated dogs declined in heart rate by 10bpm/h. Dogs treated with rabbit pheromone reduced their heart rate by24.5 bpm/h. Therefore, RP had the greatest effect in decreasing dogheart rate (FIG. 5). The observation of this decline rate difference isconsistent with the observation of the overall findings presented inFIG. 4 that heart rate average under RP was significantly lower thanPlacebo treatment.

As shown in FIG. 6, dog 1 had elevated basal heart rate and was notinfluenced by any of the treatments. All treatments generally loweredthe heart rate of dog 2, but not significantly. Dog 3 had decreasedheart rate with the rabbit pheromone spray when compared to the Placebocollar. Dog 4 had increased heart rate with the DAP collar. Therefore,with the exception of dogs 1 and 2, which were not significantlyaffected by any treatments, RP decreased the heart rates of dogs 3 and 4compared to other treatments.

Integrating Behavior and Heart Rate in Study 1

The behavior and HR data were integrated in order to extrapolate furtherinformation. Dog 1 had a very high heart rate; dogs 3, 4 and 5 hadintermediate elevated heart rate; and dogs 2, 6, 7, and 8 hadapproximately normal heart rate (around 80-120 bpm). FIG. 3 shows thatdogs 3, 5 and 7 were more active overall. Most of the increasedbehavioral activity of these three dogs was in pacing-walking. Dog 5stood or sat when it was not pacing-walking and it showed the leastamount of lying down; dog 7 showed the most pacing-walking and it sat ata moderate rate. In a sharp contrast, dogs 6 and 8 spent 100% of theirtime during the Placebo treatment lying down (inactive). Only sporadiceating and drinking were observed in these two dogs duringbaseline/Placebo observations and no defecation or urination wasobserved.

The correlation coefficient between HR and general activity was 0.34(FIG. 7), which is a moderate to weak correlation. This findingsuggested that dog heart rate was higher or lower based on more thanjust dog activity (e.g., pacing-walking) and confirms that some dogs hadnaturally elevated heart rates for reasons other than their naturalbehaviors. In addition, of the dogs that paced-walked a large amount oftime (dogs 3, 5 and 7), dogs 3 and 5 had elevated heart rate, but dog 7did not have an elevated heart rate. Dog 3 had moderately elevated heartrate during baseline/Placebo exposure. Rabbit pheromone decreased heartrate in dog 3, which was expressed by pacing-walking less (FIG. 3A).

Overall, all the collars and the spray reduced heart rate over time.This reduced heart rate was accompanied by increased sitting (FIG. 3C)in some dogs. Compared with Placebo, dogs 2 and 8 showed increasedsitting in response to the rabbit pheromone.

Study 2

In Study 2, the dogs were exposed to the same treatments as in Study 1,except a startle was also applied. An aerosol can (Pet Corrector, TheCompany of Animals, Surrey, UK) was used to make a loud hissing noiseand a spray of liquid as a startle. The protocol involved spraying theRabbit Pheromone at 0, 30, 60, and 90 min (RP; 1 μg/mL) or collarapplication (PLACEBO, SERG, or DAPC) at time zero. Each dog was startledat 45 minutes. Data were recorded for 120 minutes. Data reportingperiods were: 0 (0-30 min), 30 (30-60 min), and 90 (90-120 min).

Results as to Behavior:

The overall dog behavior after being startled once every 30 minutes fora period of 120 minutes are given in Table 9. The treatment by doginteraction was significant (P<0.01) for sitting and lying downbehaviors. As shown in Table 9, startling the dogs increased standingbehavior among RP-sprayed dogs in comparison to the dogs experiencingthe Placebo or SERG collars.

TABLE 9 Dog Behaviors During the 120 minutes After Startle (% of time)Behavior PLACEBO SERG DAPC RP SE TRT TRT*DOG TRT*HR Pace-walk 10.8 6.612.8  19.4 5.8 0.49 0.40 0.53 Standing 4.9a 3.8a   8.7^(a, b) 23.4^(b)5.3 0.06 0.14 0.14 Sitting 22.6 41.7 32.6  53.8 17.8 0.66 0.001 0.07Lying down 61.0 54.6 55.8  46.4 7.6 0.20 0.0006 0.08 Lick self 1.0a 0.0b 0.0^(b) 0.0^(b) 0.5 0.41 0.50 0.45 Eat 0.7 0.0 0.0 1.2 0.6 0.51 0.440.57 Drink 0.7 0.0 0.0 3.7 1.6 0.36 0.06 0.68 Defecate 0.3 0.0 0.3 0.00.3 0.61 0.45 0.70 Urinate 0.0 0.3 0.7 0.0 0.3 0.32 0.43 0.27Abbreviations: DAPC = Dog Appeasing Pheromone in collar form; Placebo =collar with Sergeant's Formula H; RP = Rabbit pheromone, SERG =Sergeant's collar; TRT = Pheromone/interomone treatment; HR = hour ortime.

The individual dog lying down behavior is shown in FIG. 8 and individualdog sitting behavior is shown in FIG. 9. Most dogs lay down after beingstartled; however, some dogs became more active by sitting more andlying down less after startle. For example, dogs 2, 3, 6 and 8 spentless time lying down but more time sitting after startle when RP wassprayed (FIG. 9). Dog 3 also showed less lying down and more sittingwhen DAP collar was used. Dog 2 was more active (less time lying down)and increased sitting after startle when it experienced the Serg collar(FIGS. 8 and 9). Therefore, the most common outcome for more than halfof the dogs was to increase activity by sitting more and lying down lessafter certain pheromones/interomones. Not all pheromones/interomones hadthe same effects on each dog and not all dogs responded the same to eachpheromone/interomone.

Results as to Heart Rate:

Dog heart rates in bpm (beats per minute) are shown in FIG. 10 inrelation to treatments. After startle, all dog heart rates rose forabout 10 seconds, then decreased (FIG. 10A) over a 30-minute period.Each treatment had a similar decline in heart rate over time; regressionlines/equations for the Placebo and each treatment (FIG. 10B-D) aregiven and show a similar slope over time for each treatment. None of thepheromones/interomones caused a different decline change over time ormean compared with the Placebo treatment group.

Integrating Behavior and Heart Rate in Study 2:

Because dog heart rates increased less than 5% after the startle (notethe first 10 seconds in FIG. 10), the startle was not very severe.However, in this moderate startle model, individual dogs responded inone of three ways: no change, increase lying down or increase in sittingbehavior. These behavioral responses represent a decrease in behavioralactivity with concomitant decline in heart rates over time. Althougheach pheromone/interomone ended with an apparent mean heart rate lowerthan the Placebo (at time 90 min), the treatment means did not differsignificantly from the level of the Placebo treatment group. Thus, thesepheromones/interomones did not improve the heart rates of startled dogs.

Study 3

In Study 1 and 2, the DAP was applied as a collar and the rabbitpheromone as a spray. To test if the physical form of thepheromone/interomone impacted its efficacy, Study 3 examined thebehavior and heart rate effects of Dog Appeasing Pheromone (DAP) andrabbit pheromone (RP) both applied as a spray after startle in order toobtain a direct comparison between sprays. Accordingly, Study 3 examinedthe relative effect of DAP spray (DAPS) and RP spray on the behavior andheart rate of the dog subjects. Both treatments were given to each dogin a random order. In this study, the Behavior data were collected fromdogs 1-8 while heart rate data were collected from dogs 1-4.

Results as to Behavior:

Some main effects of treatments were observed and are presented in Table10. Dogs given the RP spray tended to sit more (P=0.068) than DAPsprayed dogs. In addition, dogs sprayed with DAP both drank and urinatedmore (P<0.03) than dogs sprayed with rabbit pheromone.

TABLE 10 Dog Behavior under DAPS or RP Spray with Startle (% of time)Behavior DAP RP SE TRT TRT*DOG TRT*HR Pace-walk 6.7 9.8 13.3 0.63 0.0010.96 Standing 6.0 3.7 8.55 0.53 0.032 0.58 Sitting 15.7 35.4 5.87 0.0680.10 0.12 Lying down 49.8 43.8 39.03 0.32 0.0007 0.80 Lick self 0.42 00.037 0.68 0.630 0.44 Eat 0 0 — — — — Drink 0.17 0 0.04 0.037 0.99 0.23Defecate 0 0.93 2.51 0.17 0.0007 0.38 Urinate 0.17 0 0.04 0.037 0.9970.23

While treatment by hour interaction was not significant for anybehavior, the treatment by dog interaction was significant (P<0.05) forfour behaviors. In Study 3, dogs 1 and 4 had increased pacing-walkingafter being given rabbit pheromone (FIG. 11). This is a partialreplication of Study 1 (FIG. 3A) in that the RP spray also increasedpacing-walking of dog 1 compared with the DAP collar. Dog 3 showedincreased pacing-walking (FIG. 11) and increased standing (FIG. 12) inStudy 3 when sprayed with DAP. In contrast, dog 3 showed increasedsitting but not standing or pacing-walking in Study 1 when given the DAPcollar.

Comparing rabbit pheromone spray with DAP spray during startle, it wasnoted that DAP spray increased lying down for dogs 1, 2, and 4 comparedwith rabbit pheromone (FIG. 13). Dog 3 showed increased lying down withrabbit pheromone spray compared with DAP spray.

Results as to Heart Rate:

Surface temperatures and heart rates of dogs given rabbit pheromonespray or DAP spray are presented in FIG. 14. DAP spray and startlecaused an immediate increase in surface temperature of about 4° C. (See,FIG. 14A). After that, the surface temperature declined among DAPsprayed dogs and equaled that of rabbit pheromone sprayed dogs for 30,60 and 90 minutes after startle.

The basal heart rates declined for all dogs. In FIG. 14B, data werepresented as a change relative to time zero heart rate values. As seenin FIG. 14B, all the negative values demonstrated that heart ratesdeclined. Heart rates were generally unchanged over time, although werelower than baseline rate, for dogs sprayed with the rabbit pheromone(FIG. 14B). Heart rates declined for dogs sprayed with DAPS andstartled.

Integrating Behavior and Heart Rate in Study 3:

As seen in study 2, heart rates declined after startle. The decline inheart rate was associated, in some dogs, with an increase in lying downor sitting. Dog behavior generally reflected the heart rate data.

Study 4

In Study 4, putative pheromones were examined as room diffusers. Roomdiffusers were obtained and different liquid odors were applied over a24 hour period. In contrast to Studies 1, 2, and 3, heart rates andbehavior data were obtained over 24 hours (rather than just 2 hoursafter treatment application as in the other studies) and a baseline daywas included in the dataset. Similar to Studies 1, 2, and 3, each dogexperienced each treatment on different days in random order. Thefollowing treatment groups were evaluated: Baseline, Placebo Formula HPheromone (SERG), DAP room diffuser (DAPRD; as available commercially)and the Rabbit Pheromone in diffuser form prepared in accordance withExample 4 (RPRD, 1 μg/mL). The baseline day data were first collectedand then treatments were randomly assigned to dogs on a rotating basisuntil all dogs experienced all treatments.

Results as to Behavior:

Fewer significant behavioral effects were observed in this study than inthe previous studies (Table 11). The treatment by dog interaction wassignificant for standing and drinking behaviors (FIGS. 15 and 16). Forstanding behaviors, all treatment groups had lower (P<0.01) standingcompared with baseline (FIG. 15). For drinking behavior, dog 7 showedincreased drinking when it experienced Serg or RP room diffuser (FIG.16). DAP's effect on increased drinking (and urination) was also foundin some dogs.

TABLE 11 Dog Behavior under Room Diffuser (% of time) Behavior BaselinePlacebo SERG DAP RP SE TRT Trt*Dog Trt*Hr Pace-Walk 5.08% 7.67% 3.58%5.08% 5.67% 1.03% 0.15 0.18 0.85 Standing 3.25% 1.55% 1.83% 0.95% 1.42%0.82% 0.38 0.01 0.63 Sitting 7.46% 6.13% 4.08% 4.75% 5.00% 1.31% 0.430.28 0.81 Lying Down 83.1% 84.2% 88.9% 87.0% 87.0% 2.0% 0.30 0.15 0.87Lick self 0.00% 0.09% 0.00% 0.00% 0.09% 0.05% 0.46 0.70 0.47 Eat 0.62%0.17% 0.78% 0.69% 0.26% 0.26% 0.48 0.41 0.002* Drink 0.35% 0.12% 0.61%0.78% 0.18% 0.28% 0.42 0.007 0.52 Defecate 0.00% 0.00% 0.12% 0.18% 0.18%0.11% 0.64 0.10 0.42 Urinate 0.09% 0.09% 0.17% 0.43% 0.26% 0.13% 0.350.44 0.35

The significant (P<0.002) treatment by hour effect for eating (Table 11)is simply explained by the time required to feed and care for each dog.Because some dogs' eating fell into the next hour, the treatment by houreffect was significant only for eating. All other behaviors wereconsistent over time. Few behavioral effects and interactions wereobserved.

Results as to Heart Rate and Surface Temperature:

Heart rate data main effects are presented in Table 12. Room diffusertreatments did not impact overall dog heart rates. Dog 5 had elevatedheart rate and lower surface temperatures compared with dogs 6, 7, and 8(Table 12).

TABLE 12 Dogs Overall Heart Rate and Surface Temperatures after RoomDiffuser Treatment TREATMENT HR TEMP Baseline 80.9 34.7 Placebo 79.630.9 Form H 87.2 33.0 DAP 101.7 34.4 RP 108.4 33.8 SEP 14.9 1.14 P-value0.58 0.21 DOG NUMBER HR TEMP 5 140.6a 30.6a 6 78.4 34.4 7 81.8 32.9 865.4 35.5 SEP 13.3 1.02 P-value 0.008 0.03

As shown in FIGS. 17A and 17B, the dog by treatment effect was highlysignificant (P>0.0001) for both heart rate (HR) and surface temperature.Dog 5 had elevated HR and surface temperature when exposed to DAPpheromone or rabbit pheromone room diffusers compared with the Placebo.Dog 6 had increased heart rate and decreased surface temperature withrabbit pheromone compared with the Placebo. Dog 7's heart rate was notimpacted by treatment. However, DAP and RP increased the surfacetemperature of dog 7 compared to placebo. For Dog 8, both Serg and DAPreduced heart rate over the 24-hour period.

Integrating Behavior and Heart Rate in Study 4—Room Diffusers:

Dog 5 was the only dog most impacted by the Room Diffuser treatmentsapplied. Its heart rate increased to about 200 bpm and its surfacetemperature increased between 2° C. to 5° C. when it experienced DAP orRP as a room diffuser (FIGS. 17A and 17B). Other effects on heart ratewere much smaller in magnitude. Dog 7's increase in surface temperature,from RP or DAP room diffusers, was not correlated with any measuredbehavior change.

OVERALL CONCLUSIONS

Three delivery methods were examined (collar, spray, and room diffuser)and conclusions may be drawn about their efficacy. First, the pheromoneswere similar in efficacy when applied as a collar or spray. When used asa room diffuser, the pheromones/interomones had fewer significanteffects compared with when they were delivered in collar or spray form.

All four studies indicated that pheromones and interomones havesignificant effects on the physiology and behavior of dogs.Meta-analyses were performed across studies to identify potentialover-arching effects (FIGS. 18A and B). Only dog sitting behavior wasincreased by the use of rabbit interomone. The reaction of most dogs tohandling or startle was to go lay down; but the dogs exposed to rabbitinteromone were more likely to sit. Other than this general effect, eachother finding must be considered within the context of the form ofdelivery (spray, collar or room diffuser) and the response of individualdog.

It was notable that no dog licked itself during the baseline period orunder placebo in Study 1 (Tables 7 and 8). When dogs were startled inStudy 2, the placebo dogs licked themselves (Table 9), but dogs in eachtreatment group had “lick self” values of zero. Therefore, one couldconclude that each pheromone or interomone reduced or eliminatedstartle-induced licking of self in dogs.

Dogs 3, 5, and 7 paced during the baseline data collection. Theyaveraged from 19% to 50% of their time pacing (Table 7) while the otherfive dogs did not pace during baseline data collection. Dog 1 beganpacing at a high rate when exposed to DAP (FIG. 3A). Dog 3 increasedpacing with Serg, but reduced its pacing with DAP collar and rabbitinteromone spray. Dog 5 was largely unaffected by anypheromone/interomone. Dog 7's pacing was reduced by DAP collar andreduced even more by rabbit interomone spray (FIG. 3A).

Eating, drinking, urinating and defecating were highly correlated anddependent upon how the dogs were managed. Examination of these behaviorsin Table 7 showed that only some dogs exhibited these behaviors. Only inStudy 4 was the treatment by dog interaction significant for drinkingbehavior. DAP and Serg tended to increase dog water drinking when thesepheromones were in room diffuser form or (in a non-significant way, butgreater than zero) after dogs were startled.

Among the various pheromones, the rabbit interomone had the mostconsistent or largest effect on dog behavior and physiology.

Example 7 Determining Efficacy of a Collar Containing Rabbit InteromoneCompared to Pheromone Collars

The objective of this study was to compare the efficacy of two pheromonecollars (Ceva Dog Appeasing Pheromone Collar (DAP) and Sergeant'spheromone collar (Sentry or Meridian brands) with the new rabbitinteromone collar (prepared in accordance with Example 2) and allagainst a Placebo. Four male dogs were used as test subjects. Each dogwas clinically diagnosed as “anxious” dogs by a veterinarian boarded inanimal behavior (Dr. Valerie Tynes). Dogs were kept one per room. Therooms were spacious (10′6″×17′8″). Each dog had a water bowl, was fedonce per day ad libitum and had access to at least one toy on acontinual basis. Heart rate and surface temperature were measured bytelemetry.

The study was conducted in two phases: Baseline and after startle. Inthe baseline study each of the four dogs received each collar treatmentin random order for two days at a time. Heart rate and surfacetemperature were collected each 5 seconds for 24 hours. In the secondphase, dogs were startled with a 110 dB Fog Horn and heart rate wasmeasured each 1 second for 10 minutes before and 2 hours after startle.

Heart rate data are presented in FIGS. 19-21. The overall heart ratedata did not show a significant treatment effect. However, the Treatmentby Dog interaction approached significance (P=0.10). These data arepresented in FIG. 19. The data indicate that dogs' heart rates respondeddifferently to treatments. The RP collar increased the heart rate of dog1 and the DAP collar increased the heart rate of dog 4. The Sergeant'scollar also increased the heart rate of dog 4 compared to Placebo, butless than with the DAP collar.

Dogs were startled with the Fog Horn. The startle typically increasesheart rate and then it declines. The rate of decline is proportional tothe degree to which the anxious dog benefited from thepheromone/interomone. FIG. 20 illustrates that Dog by Treatmentinteraction was significant (P=0.046). Dogs 1 and 4 had reduced heartrate from Serg and RP collars. DAP reduced heart rate only in dog 1.After startle, DAP significantly increased heart rate in dog 4.

FIG. 21 illustrates the rate of decline in heart rate in the hour of thestartle (hour 1) and in the next hour (hour 2). The slope of the line(the value before the x in the regression equation) indicates thedecline in heart rate. The placebo-collared dogs' heart rate declined 15beats per minute (bpm) and RP-collared dogs' heart rate declined 26.6bpm.

Example 8 Determining Efficacy of a Rabbit Pheromone as Interomone in aCollar to Modulate Heart Rate in Anxious Dogs Compared to a PheromoneOnly Collar and an Interomone/Pheromone Combined Collar

Dogs diagnosed as being “nervous” were treated with four differenttreatments on different days: Placebo collar, Pheromone only collar(Serg), Rabbit interomone collar (RP), and Interomone Plus Pheromonecollar (Serg+RP). Each dog experienced a given collar for 24 hours.Heart rate of the dogs was measured by remote telemetry. Data acquiredduring basal testing are presented in FIGS. 22 and 23. FIG. 22illustrates the effects of the collars on heart rate collected over aperiod of 24 hours. Both Serg and RP increased heart rate, but thecombined effect of Serg and RP was not different than the placebo.

Each dog experienced a loud noise (fog horn) during a 2 second blast.The noise startled the dogs. Each dog had the collar on before, duringand after the startle experience. Data are summarized in FIGS. 24A, 24Band 25. FIG. 24A shows main effects of Serg and RP. Dogs with Sergcollar did not differ from the control. Dogs with the RP collar hadlower heart rate during startle compared to control dogs. The dataillustrates that Serg alone had no effect on the startled dog heartrate. Either RP alone or with Serg had reduced heart rate. The datafurther indicate that only the RP is effective in reducing the heartrate of startled dogs.

Example 9 Determining Efficacy of Rabbit Pheromone as Interomone in aCollar to Modulate Heart Rate in Anxious Dogs

The objective of this study was to assess efficacy ofpheromones/interomones to modulate heart rate and behavior in adultanxious dogs (trembling, cowering, shy). The dogs (8.1±0.18 kg;estimated 5-12 yr intact males) were obtained from a local researchfacility. Body weights and feed intake were recorded. Each dog washoused in a separately ventilated room with a minimum of 12 m² of floorspace. Heart rate (HR) and surface temperature was measured using atelemetry system (Data Science International, St. Paul, Minn.). Behaviorwas recorded on a DVR and later reviewed by a trained individual. A scansample was used with a recording interval of 5 min over 24 hours.

The dogs were treated with four different treatments on different days:Placebo collar (no Pheromone/Interomone), Pheromone only collar (SERG),Rabbit pheromone as interomone collar (RP), and Interomone plusPheromone collar (SERG+RP). At the end of 24 hours with a given collar,each dog was startled with a 110 db foghorn placed 12 cm from the dog'shead while behavior and heart rate were recorded. Each dog received eachtreatment in a Latin square design with repeated measures over time.This model allowed evaluation of effects of treatment, dog, treatment bydog, time, treatment by time and dog by time.

Baseline HR did not differ among treatments (avg=110.1±13.3 bpm). Afterstartle, the RP lowered (P<0.01) HR compared with placebo (124.5±7.2 vs.157.8±7.2 bpm); however, the treatment by dog interaction (P<0.01)indicated certain dogs were more responsive than others. Dogs with RPcollars spent more time lying down (87.4±5.4 vs. 63.2±4.8% of time,P=0.01) and less time pacing (3.0±0.2 vs. 3.8±0.02%, P<0.05) thanplacebo-treated dogs. Pace/walk changed differentially among treatmentsand dogs (dog by RP and SERG effects for pace/walk, P=0.05).

In summary, RP lowered HR while SERG and SERG+RP did not change dog HR.However, pheromone/interomone treatments had differential effects onindividual dog behavior and HR. Pheromones/interomones can causemeaningful changes in dog behavior and HR among certain anxious dogs.

Example 10 Administration of a Collar Containing 2-methylbut-2-enal toCats

A collar containing 2-methylbut-2-enal can be prepared in accordancewith Example 3. The resultant collar, when worn by a cat, will cause thecat to exhibit a significant change in behavior towards a calmerdemeanor.

One skilled in the art would readily appreciate that the methods,compositions, and products described herein are representative ofexemplary embodiments, and not intended as limitations on the scope ofthe invention. It will be readily apparent to one skilled in the artthat varying substitutions and modifications may be made to the presentdisclosure disclosed herein without departing from the scope and spiritof the invention.

All patents and publications mentioned in the specification areindicative of the levels of those skilled in the art to which thepresent disclosure pertains. All patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated as incorporatedby reference.

The present disclosure illustratively described herein suitably may bepracticed in the absence of any element or elements, limitation orlimitations that are not specifically disclosed herein. Thus, forexample, in each instance herein any of the terms “comprising,”“consisting essentially of,” and “consisting of” may be replaced witheither of the other two terms. The terms and expressions which have beenemployed are used as terms of description and not of limitation, andthere is no intention that in the use of such terms and expressions ofexcluding any equivalents of the features shown and described orportions thereof, but it is recognized that various modifications arepossible within the scope of the present disclosure claimed. Thus, itshould be understood that although the present disclosure has beenspecifically disclosed by preferred embodiments and optional features,modification and variation of the concepts herein disclosed may beresorted to by those skilled in the art, and that such modifications andvariations are considered to be within the scope of this invention asdefined by the appended claims.

What is claimed is:
 1. A composition administered to an animal for the modification of behavior, the composition comprising from between about 0.001% and about 1% (w/w) of an interomone and between about 0.5% and 99.99% (w/w) of at least one carrier solvent, wherein the amount of interomone administered to the animal is between about 1.0 pg/mL to about 1.0 g/mL.
 2. The composition of claim 1, wherein the interomone is 2-methylbut-2-enal.
 3. The composition of claim 2, wherein 2-methylbut-2-enal is present in an amount from between about 0.01% and about 0.1% (w/w) of the composition.
 4. The composition of claim 1, wherein the at least one solvent is selected from the group consisting of lipophilic organic diluents, alcohols, ethylene glycol, propylene glycol, dipropylene glycol, ether, chloroform, benzene, carbon disulfide, non-volatile oils, volatile liquids, water, and combinations thereof.
 5. The composition of claim 4, wherein the at least one solvent comprises an alcohol selected from the group consisting of ethanol, propanol, isopropanol, butanol, pentanol, hexanol, heptanol, octanol, and phenyl ethyl alcohol.
 6. The composition of claim 5, wherein the alcohol is selected from the group consisting of ethanol or isopropanol.
 7. The composition of claim 4, wherein the alcohol is present in the composition from between about 1% (w/w) and about 20% (w/w) of the composition.
 8. The composition of claim 4, wherein the at least one solvent comprises water.
 9. The composition of claim 8, wherein water is present in the composition from between about 70% and about 99.99% (w/w) of the composition.
 10. The composition of claim 1, wherein the composition further comprises an additional component selected from the group consisting of a surfactant, a thickener, a fragrance, and combinations thereof.
 11. The composition of claim 1, wherein the composition further comprises at least one additional pheromone or pheromone composition.
 12. The composition of claim 1, wherein the animal is selected from the group consisting of a dog, a cat, a horse, and a snake.
 13. The composition of claim 1, wherein the composition is administered in the form of a spray, a diffuser, or a slow release matrix.
 14. A method of modifying behavior in a positive manner in an animal comprising: administering an interomone composition to the animal for a period of time, the composition comprising between about 0.001% and about 1% (w/w) of an interomone and between about 0.5% and 99.99% (w/w) of at least one carrier solvent, wherein the amount of interomone administered to the animal is between about 1.0 pg/mL to about 1.0 g/mL, and wherein the animal is selected from the group consisting of a dog, a cat, a horse, and a snake.
 15. The method of claim 14, wherein the interomone comprises 2-methylbut-2-enal.
 16. The method of claim 14, wherein the method of administration is inhalation administration.
 17. The method of claim 14, wherein the composition is formulated as a spray, a diffuser, or a slow release matrix.
 18. The method of claim 17, wherein administering the spray composition comprises spraying the animal or spraying the animal's environment with the composition.
 19. The method of claim 14, wherein the period of time is at least one second.
 20. The method of claim 14, wherein the period of time is at least one week.
 21. The method of claim 14, wherein the period of time is at least one month.
 22. The method of claim 14, wherein the composition comprises at least one additional pheromone or pheromone composition.
 23. A method of modifying behavior in a positive manner in an animal comprising: administering an effective amount of an interomone spray composition to the animal for a period of time, the spray composition comprising about 0.01% (w/w) 2-methylbut-2-enal, about 10% (w/w) isopropyl alcohol, and about 89.49% (w/w) water, wherein the animal is selected from the group consisting of a dog, a cat, and a horse.
 24. A method of modifying behavior in a positive manner in an animal comprising: administering an effective amount of an interomone diffuser composition to the animal for a period of time, the diffuser composition comprising about 0.02% (w/w) 2-methylbut-2-enal, about 15% (w/w) isopropyl palmitate, and about 84.48% (w/w) silicone fluid, wherein the animal is selected from the group consisting of a dog, a cat, and a horse.
 25. A method of modifying behavior in a positive manner in an animal comprising: administering an effective amount of an interomone slow release matrix composition to the animal for a period of time, the slow release matrix composition comprising about 0.02% (w/w) 2-methylbut-2-enal, and about 99.780% (w/w) copolymer, wherein the animal is selected from the group consisting of a dog, a cat, and a horse. 